Departments of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131,USA.
Infect Immun. 2011 Jul;79(7):2737-45. doi: 10.1128/IAI.01146-10. Epub 2011 Apr 11.
Gastric epithelial cells (GECs) express the class II major histocompatibility complex (MHC) and costimulatory molecules, enabling them to act as antigen-presenting cells (APCs) and affect local T cell responses. During Helicobacter pylori infection, GECs respond by releasing proinflammatory cytokines and by increasing the surface expression of immunologically relevant receptors, including class II MHC. The CD4(+) T cell response during H. pylori infection is skewed toward a Th1 response, but these cells remain hyporesponsive. Activated T cells show decreased proliferation during H. pylori infection, and CD4(+) CD25(+) FoxP3(+) regulatory T cells (Tregs) are present at the site of infection. In this study, we examined the mechanisms surrounding the CD4(+) T cell responses during H. pylori infection and found that transforming growth factor β (TGF-β) plays a major role in these responses. GECs produced TGF-β1 and TGF-β2 in response to infection. Activated CD4(+) T cells in culture with H. pylori-treated GECs were decreased in proliferation but increased upon neutralization of TGF-β. Naïve CD4(+) T cell development into Tregs was also enhanced in the presence of GEC-derived TGF-β. Herein, we demonstrate a role for GEC-produced TGF-β in the inhibition of CD4(+) T cell responses seen during H. pylori infection.
胃上皮细胞 (Gastric epithelial cells, GECs) 表达 II 类主要组织相容性复合体 (major histocompatibility complex, MHC) 和共刺激分子，使它们能够充当抗原呈递细胞 (antigen-presenting cells, APCs)，并影响局部 T 细胞反应。在幽门螺杆菌 (Helicobacter pylori, H. pylori) 感染期间，GECs 通过释放促炎细胞因子和增加免疫相关受体（包括 II 类 MHC）的表面表达来做出反应。在 H. pylori 感染期间，CD4+ T 细胞反应偏向于 Th1 反应，但这些细胞仍然反应低下。在 H. pylori 感染期间，激活的 T 细胞显示增殖减少，并且感染部位存在 CD4+ CD25+ FoxP3+ 调节性 T 细胞 (regulatory T cells, Tregs)。在这项研究中，我们检查了 H. pylori 感染期间 CD4+ T 细胞反应的机制，并发现转化生长因子 β (transforming growth factor β, TGF-β) 在这些反应中起主要作用。GECs 对感染产生 TGF-β1 和 TGF-β2。在与用 H. pylori 处理的 GEC 共培养的激活的 CD4+ T 细胞中，增殖减少，但中和 TGF-β 后增加。在 GEC 衍生的 TGF-β 存在下，幼稚 CD4+ T 细胞向 Tregs 的发育也得到增强。在此，我们证明了 GEC 产生的 TGF-β 在抑制 H. pylori 感染期间观察到的 CD4+ T 细胞反应中的作用。
